Method for in vitro activation and/or expansion of immune cells

Abstract

A method for in vitro activation and/or expansion of immune cells is provided, including the steps of: a) providing magnetic particles having multi-protrusive surface modified with at least one type of immuno-inducing substance, in which each magnetic particle includes a copolymer core, a polymer layer, a magnetic substance layer, and a silicon-based layer from the inside to the outside; b) providing a cell solution including at least one type of immune cell in the cell solution; and c) bringing the magnetic particles in contact with the cell solution, in which the at least one type of immuno-inducing substance on the surface of the magnetic particle activates and/or expands the at least one type of immune cell in the cell solution.

What is claimed is: 
     
       1. A method for in vitro activation and/or expansion of immune cells, comprising:
 a) providing magnetic particles, wherein surfaces of each of the magnetic particles are multi-protrusive and modified with at least one type of immuno-inducing substance, and wherein each of the magnetic particles comprises a copolymer core, a polymer layer, a magnetic substance layer, and a silicon-based layer from the inside to the outside; 
 b) providing a cell solution, wherein the cell solution comprises at least one type of immune cell; and 
 c) bringing the magnetic particles in contact with the cell solution such that the at least one type of immuno-inducing substance on the surface of each of the magnetic particles activates and/or expands the at least one type of immune cell in the cell solution, wherein surfaces of the copolymer core comprise a plurality of protrusions which are irregularly shaped, and the average height of the plurality of protrusions that is the average value of a vertical distance of a top side of each protrusion to a connection line between two bottom sides of each protrusion is 300 nm to 1000 nm. 
 
     
     
       2. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the average diameter of each of the magnetic particles is 1 μm to 50 μm. 
     
     
       3. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the at least one type of immune cell comprises a T cell, a NK cell, or a combination thereof. 
     
     
       4. The method for in vitro activation and/or expansion of immune cells of  claim 3 , wherein the at least one type of immune cell comprises a regulatory T cell. 
     
     
       5. The method for in vitro activation and/or expansion of immune cells of  claim 4 , wherein the at least one type of immune cell comprises an αβ T cell, a γδ T cell, or a combination thereof. 
     
     
       6. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the at least one type of immune cell comprises a γδ T cell. 
     
     
       7. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the at least one type of immuno-inducing substance comprises an anti-CD3 antibody and an anti-CD28 antibody. 
     
     
       8. The method for in vitro activation and/or expansion of the immune cells of  claim 1 , wherein the surface of each of the magnetic particles is modified with the at least one type of immuno-inducing substance through non-covalent binding, covalent binding, avidin-biotin interaction, electrostatic adsorption, hydrophobic adsorption, or a combination thereof. 
     
     
       9. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the copolymer core comprises a copolymer obtained by copolymerizing a monofunctional monomer and a bifunctional monomer. 
     
     
       10. The method for in vitro activation and/or expansion of immune cells of  claim 9 , wherein the volume percentage of the bifunctional monomer relative to the monofunctional monomer is 0.4% to 2%. 
     
     
       11. The method for in vitro activating and/or expansion of immune cells of  claim 1 , wherein the copolymer core comprises a styrene/divinylbenzene copolymer, a methyl methacrylate/triethylene glycol dimethacrylate copolymer, a methyl methacrylate/ethylene glycol dimethacrylate copolymer, a styrene/triethylene glycol dimethacrylate copolymer, a styrene/ethylene glycol dimethacrylate copolymer, or a methyl methacrylate/divinylbenzene copolymer. 
     
     
       12. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the polymer layer comprises at least one charged functional group. 
     
     
       13. The method for in vitro activation and/or expansion of immune cells of  claim 12 , wherein the at least one charged functional group comprises a carboxyl group, an amine group, or a combination thereof. 
     
     
       14. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the magnetic substance layer comprises a paramagnetic substance, a superparamagnetic substance, a ferromagnetic substance, a ferrite magnetic substance, or a combination thereof. 
     
     
       15. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein the magnetic substance layer comprises an iron ion (Fe2+), a cobalt ion (Co2+), a nickel ion (Ni2+), or a combination thereof. 
     
     
       16. The method for in vitro activation and/or expansion of immune cells of  claim 1 , wherein a thickness of the silicon-based layer is at least 1 nm to 50 nm.